Cell Injury Adaptation And Cell Death

Adaptation mechanisms and Cell injury

LEARNING OBJECTIVES

• Understand the concept of cell and tissue adaptation:
• 1.Hypertrophy (increase in size of cell)
• 2.Hyperplasia (increase in number of cells)
• 3.Atrophy (shrinkage in size of cell)
• 4.Metaplasia (change of shape of cell)

5.Dysplasia (disorderly growth)

…..

• Describe the causes of cell injury
• Know types of cell death & their clinical examples:
• 1.Apoptosis= programmed death (physiologic & pathologic)

2.Necrosis= group cell death (pathologic)

Differentiate between apoptosis & necrosis

CELLULAR ADAPTATIONs TO STIMULI

Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment.

Physiologic adaptations: Usually represent responses of cells to normal stimulation by hormones or endogenous chemical mediators (e.g. the hormone-induced enlargement of the breast and uterus during pregnancy).

Pathologic adaptations: are responses to stress that allow cells to modulate their structure and function and thus escape injury.

Such adaptations can take several distinct forms.

Five (5) types of cellular adaptations

• 1.Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia

Dysplasia

Types of cellular adaptations….

1.Atrophy

It is a decrease in the size (shrinkage) of the cell, tissue or organ which is brought by decrease in substances within cells. Atrophic cells may have diminished function but are not dead.

Atrophy as other cell adaptations can be classified as either physiological or pathological.

• Physiologic atrophy occurs with aging and involved essentially all organs in the body
• Examples:
• 1.Decrease in breast glandular tissues after menopause
• 2.Decrease in size of uterus after child birth (parturition)

3.Decrease in size of brain tissue of advanced aged man 4.The decrease of thymus tissue after puberty which remains essentially as fibrous tissue.

Cell Injury Adaptation And Cell Death

Pathological atrophy occur as a result of lack of inadequate nutrients (ischaemia), innervations of an organ, disuse of an organ (lack of exercise after long term of inability) and loss of endocrine stimulation.

• Example:

Hypogonadism

Causes of atrophy

• A decreased workload (e.g. immobilization of a limb to permit healing of a fracture)
• Loss of innervations
• Diminished blood supply
• Inadequate nutrition
• Loss of endocrine stimulation

Aging ( leads to senile atrophy)

2.HYPERTROPHY

Hypertrophy and hyperplasia can also occur together, and obviously both result in an enlarged (hypertrophic) organ.

Examples:

1.The massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogen-stimulated smooth muscle hypertrophy and smooth muscle hyperplasia.

• Increase in muscle mass in weightlifter

3.Pathological hypertrophy can also be demostrated in the heart.

Myocardium subjected to persistent increased load, as in hypertension or with a stenosis valve, adapts by undergoing hypertrophy-an increase in the size of the individual cells and ultimately the entire heart-to generate the required higher contractile force.

Hypertrophic cardiomyopathy

3.HYPERPLASIA

It is an increase in the number of cells in an organ or tissue usually results in increased size of the organ or tissue. ! Although hypertrophy and hyperplasia are two distinct processes, both frequently occur together and they may be triggered by the same external stimulus. !

• Physiologic hyperplasia can be divided into :-
• -Hormonal hyperplasia which increases the functional capacity of a tissue when needed.

-Compensatory hyperplasia which increases tissue mass after damage or partial resection.

Examples: (physiological hyperplasia)

1.Increase in breast glandular tissue during pregnant 2.When a liver is partially resected, mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver to its normal weight.

After restoration of the liver mass, cell proliferation is turned off by various growth inhibitors.

Pathological hyperplasia is caused by excessive hormonal stimulation or growth factors on target cells.

• Examples
• 3.Benign prostate hyperplasia (BPH)
• 4.Endometrial hyperplasia

Hyperplasia is an adaptive response in cells capable of replication.

Hyperplasia is also an important response of connective tissue cells in wound healing, in which proliferating fibroblasts and blood vessels aid in repair.

4.METAPLASIA

Is a reversible change in which one mature differentiated cell type (epithelial or mesenchymal) is replaced by another mature differentiated cell type.

In this type of cellular adaptation, cells sensitive to a particular stress are replaced by other cell types better able to withstand the stressful environment.

Examples:

1.Epithelial metaplasia is exemplified by the squamous change that occurs in the respiratory epithelium in habitual cigarette smokers.

The normal ciliated columnar epithelial cells of the trachea and bronchi are focally or widely replaced by stratified squamous epithelial cells.

2.Vitamin A deficiency may also induce squamous metaplasia in the respiratory epithelium.

Squamous metaplasia in respiratory epithelia of a cigarette smoker

Cell Injury Adaptation And Cell Death

However, the influences that induce metaplastic transformation, if persistent, may predispose to malignant transformation of the epithelium. o In a common form of lung cancer, squamous metaplasia of the respiratory epithelium often coexists with cancers composed of malignant squamous cells.

5.DYSPLASIA

Means disordered growth.

Dysplasia is encountered principally in epithelia and is characterized by loss in the uniformity of individual cells as well as a loss in their architectural orientation.

Examples of dysplasia

• Achondroplasia
• Fibrous dysplasia

Cervical dysplasia (can become cervical cancer)

Fibrous dysplasia Achondroplasia

CELL INJURY

Cell injury or cell demage refers to a variety of changes of stress that a cell suffers due to external or internal environmental changes.

When cells are injured, one of two patterns must dominate: reversible cell injury leading to adaptation of the cell and tissue, or irreversible cell injury leading to cell death and tissue damage.

Reversible cell injury:

In early stages or mild forms of injury the functional and morphologic changes are reversible if the damaging stimulus is removed.

At this stage, although there may be significant structural and functional abnormalities, the injury has typically not progressed to severe membrane damage and nuclear dissolution. E.g fatty liver Irreversible cell injury:

With continuing damage, the injury becomes irreversible, at which time the cell cannot recover and it dies.

Types of cell death

Necrosis is the major pathway of cell death in many commonly encountered injuries, such as those resulting from ischemia, exposure to toxins, various infections, and trauma.

• necrosis is always a pathologic process

Apoptosis (programmed cell death)

When a cell is deprived of growth factors or the cell’s DNA or proteins are damaged beyond repair, the cell kills itself by another type of death, called apoptosis. which is characterized by nuclear dissolution without complete loss of membrane integrity.

Apoptosis is an active, energy-dependent, tightly regulated type of cell death that is seen in some specific situations.

Apoptosis serves many normal functions and is not necessarily associated with pathologic cell injury.

Examples of physiological apoptosis

1.Involution of hormone-dependent tissues upon hormone deprivation, such as endometrial cells breakdown during the menstrual cycle

• Regression of the lactating breast after weaning.

DIFFERENCES BETWEEN APOPTOSIS AND NECROSIS

Necrosis versus Apoptosis